Transperineal ultrasonography in perianal Crohn's disease and recurrent cryptogenic fistula-in-ano.

AIM: Successful anal fistula care is aided by specialized imaging accurately defining the site of the internal opening and fistula type. Imaging techniques are complementary, designed to answer specific anatomical questions. There are limited data concerning the clinical value of transperineal ultrasound (TP-US) in both cryptogenic fistula-in-ano and perianal Crohn's disease (PACD). The aim of the study was to assess the accuracy of TP-US compared with operative findings in patients with perirectal sepsis. METHOD: Patients with recurrent cryptogenic anal fistula and PACD referred for sonography were examined using TP-US by a single examiner blinded to the operative results. Fistulae were categorized by the Parks classification predicting the site of the internal fistula opening. Ancillary horseshoe collections, abscesses and secondary tracks were defined. RESULTS: Fourteen patients with PACD and 27 patients with recurrent cryptogenic fistula-in-ano were analysed with comparative images and operative data. Correlation of fistula type for cryptogenic and PACD patients respectively was 23/27 (85.2%) and 12/14 (85.7%), with a correlative internal opening site (when found at surgery) of 16/22 (72.3%) and 12/14 (85.7%). Misclassification of fistula type in cryptogenic cases occurred in the presence of ancillary abscesses with associated acoustic shadowing. In PACD patients, TP-US was used when anal stenosis precluded endoanal ultrasonography, assisting in the diagnosis of recto-vaginal fistulae. CONCLUSION: TP-US is a useful complementary technique to assess fistula-in-ano and has special advantage when there is anal canal distortion, complex fistula type or suspicion of a recto-vaginal fistula.

Ultrasound in the investigation of posterior compartment vaginal prolapse and obstructed defecation.

Recent developments in diagnostic imaging have made gynecologists, colorectal surgeons and gastroenterologists realize as never before that they share a common interest in anorectal and pelvic floor dysfunction. While we often may be using different words to describe the same phenomenon (e.g. anismus/vaginismus) or attributing different meanings to the same words (e.g. rectocele), we look after patients with problems that transcend the borders of our respective specialties. Like no other diagnostic modality, imaging helps us understand each other and provides new insights into conditions we all need to learn to investigate better in order to improve clinical management. In this review we attempt to show what modern ultrasound imaging can contribute to the diagnostic work-up of patients with posterior vaginal wall prolapse, obstructed defecation and rectal intussusception/prolapse. In summary, it is evident that translabial/perineal ultrasound can serve as a first-line diagnostic tool in women with such complaints, replacing defecation proctography and MR proctography in a large proportion of female patients. This is advantageous for the women themselves because ultrasound is much better tolerated, as well as for healthcare systems since sonographic imaging is much less expensive. However, there is a substantial need for education, which currently remains unmet.

Ultrasonographic assessment of patients referred with chronic anal pain to a tertiary referral centre.

BACKGROUND: Chronic anal pain is relatively common as a presentation to specialist physicians and surgeons. Currently, it is regarded as a functional disorder upon the exclusion of occult intersphincteric sepsis. Our study assessed an unselected cohort of patients presenting with chronic previously undiagnosed anal pain using routine ultrasonography. METHODS: All patients referred to a tertiary gastroenterology service between January 2005 and January 2008 with a diagnosis of chronic anal pain (>3 months duration with no clinical anorectal signs) underwent endoanal and static and dynamic transperineal ultrasound to assess for the frequency and pattern of occult intersphincteric sepsis. RESULTS: Of 1,580 patients referred, there were 146 presenting with chronic anal pain as a main symptom. Of these, 37 (25.3%) had intersphincteric sepsis (ISS) diagnosed with ultrasound examination with 17 undergoing evaluable surgery. There was a male preponderance (70.3%) with the diagnosis being made in 46% of cases after 6 months of symptoms and with 80.8% having posteriorly located sepsis. This occurred on a background of 62% having previous acute proctological conditions. There was complete ultrasonographic and operative concordance with 15 becoming asymptomatic after surgery at a mean follow-up of 6 months. CONCLUSION: Occult intersphincteric sepsis is not uncommon and is diagnosed using routine ultrasonography at the time of clinical presentation. Endoanal and transperineal ultrasound is recommended as part of the investigative armamentarium to exclude categorization as functional anorectal pain. This is currently not part of the Rome III coding for such a diagnosis suggesting a revision of these diagnostic criteria for the ultimate diagnosis of functional proctalgia.

Effect of Flavobacterium columnare inoculation, antibiotic treatments and resident bacteria on rainbow trout Oncorhynchus mykiss eyed egg survival and external membrane structure.

This study was conducted to evaluate the potential pathogenicity of the bacterium Flavobacterium columnare on rainbow trout Oncorhynchus mykiss eyed eggs. Survival to hatching was unaffected by the inclusion in the incubation water of either 300 colony-forming units (CFU) ml(-1) or 3000 CFU ml(-1) of F. columnare at either 10 or 12 degrees C in either McConaughy or Shasta strain eyed eggs. Bacterial numbers, obtained via scanning electron microscopy or culture, and external membrane morphology were also not significantly different among eggs receiving different concentrations of F. columnare. Initial F. columnare burdens were significantly and positively correlated to the presence of biofilm on the egg external membrane, and biofilm was in turn significantly correlated with increased membrane degradation. The use of either streptomycin or tetracyclin antibiotics significantly reduced bacterial numbers on McConaughy strain eggs, and more eggs survived to hatch in those dishes treated with antibiotics.

Effects of angiotensin II generated by an angiotensin converting enzyme-independent pathway on left ventricular performance in the conscious baboon.

Human chymase is a serine proteinase that converts angiotensin (Ang) I to Ang II independent of angiotensin converting enzyme (ACE) in vitro. The effects of chymase on systemic hemodynamics and left ventricular function in vivo were studied in nine conscious baboons instrumented with a LV micromanometer and LV minor axis and wall thickness sonomicrometer crystal pairs. Measurements were made at baseline and after [Pro11DAla12] Ang I, a specific substrate for human chymase, was given in consecutive fashion as a 0.1 mg bolus, an hour-long intravenous infusion of 5 mg, a 3 mg bolus, and after 5 mg of an Ang II receptor antagonist. [Pro11DAla12]Ang I significantly increased LV systolic and diastolic pressure, LV end-diastolic and end systolic dimensions and the time constant of LV relaxation and significantly decreased LV fractional shortening and wall thickening. Administration of a specific Ang II receptor antagonist reversed all the hemodynamic changes. In separate studies, similar results were obtained in six of the baboons with ACE blockade (20 mg, intravenous captopril). Post-mortem studies indicated that chymase-like activity was widely distributed in multiple tissues. Thus, in primates, Ang I is converted into Ang II by an enzyme with chymase-like activity. This study provides the first in vivo evidence of an ACE-independent pathway for Ang II production.

Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting highly immunized patients.

BACKGROUND: Highly immunized patients are a challenge for organ transplantation programs. One way of increasing the likelihood of transplantation in this group of patients is to expand the possible donations by defining acceptable HLA mismatches. In the Scandiatransplant Acceptable Mismatch Program (STAMP), a de-centralized approach has been implemented in 2009. AIMS: The program has been improved during the years from utilizing HLA-A, -B, -DR matching only to include typing of all deceased donors for HLA-A, -B, -C, -DRB1 and -DQB1. The calculation of a transplantability score (TS) has been introduced in order to take both HLA and AB0 into consideration resulting in a more realistic picture of the transplantability chance. MATERIALS AND METHODS: Patients were selected for eligibility and results of immunisation status were prepared in each of the 9 tissue typing laboratories, while access to the program is finally governed by a common steering group of immunologists and clinicians. RESULTS: In the period from March 2009 until February 2015, 96 patients were transplanted within this program. The mean recipient age was 49 years and 57% were females, 30% of the patients were first transplants and of these 93% were females. The majority of the patients had 2-5 HLA-A, -B. -DR mismatches. The allograft survival at 60 months was 79.1%. Applying the TS to the cohort confirmed that patients with a low TS score had longer waiting times. CONCLUSION: The program has matured during the years and now proves to be a valid approach for transplanting highly immunized patients.

Infectious complications after multivisceral transplantation in adults.

UNLABELLED: It is thought that multivisceral transplantation requires high levels of immunosuppression and therefore, patients run an increased risk of infection. We retrospectively reviewed our center's experience with clinically relevant infectious complications. PATIENTS: Between 2000 and 2005, 10 adult patients underwent multivisceral transplantation. Two immunosuppression protocols were used: between 2000 and 2003, a high immunosupression protocol (six patients; daclizumab induction, tacrolimus trough levels >20 ng/mL and steroids) and an immunomodulatory, low imunosuppression scheme from 2003 onward (four patients; ATG induction, tacrolimus levels 5 to 10 ng/mL, no steroids). Standard antimicrobial prophylaxis consisted of vancomycin, meropenem, and amphotericin B. Cytomegalovirus (CMV) prophylaxis was used in all but first two cases. Donor and recipient CMV status were D+/R+ (n = 7), D+/R- (n = 2), D-/R+ (n = 1). RESULTS: The median follow-up period was 627 days (range, 19 to 2207 days). A total of 47 infectious episodes were recorded in all patients (range 1 to 14 per patient). The etiology was bacterial in 32 (69%), viral in 8 (17%), and fungal in 7 (14%) cases. The most frequent were catheter related (n = 13) followed by respiratory (n = 7), intraabdominal (n = 6), and wound infections (n = 5). Symptomatic viral infection of the graft (CMV gastritis or enteritis, adenoviral enteritis) was also encountered. Epstein-Barr virus was transiently detected in the serum of nine patients, one of whom later developed posttransplant lymphoproliferative disorder (PTLD). Three deaths all among patients receiving high immunosuppression were owing to infectious complications: pulmonary PTLD at 4 months posttransplantation, ruptured mycotic aneurysm after 8 weeks, and sepsis after 3 weeks. CONCLUSIONS: Infections accounted for a high morbidity after multivisceral transplantation, representing the leading cause of mortality. Exhaustive monitoring, early antimicrobial intervention, and lower immunosuppression may improve the outcome.

Laser-Doppler flowmetry in the monitoring of the human intestinal allograft: a preliminary report.

During acute rejection, graft endothelium becomes a prime target for recipient immune cells. Animal studies have shown reduced microvascular perfusion, probably due to increased endothelial-leukocyte interaction and endothelial impairment, leading to graft damage. Using laser-Doppler flowmetry (LDF), we correlated the microvascular blood flow in the intestinal mucosa of five patients receiving multivisceral grafts with clinical events and pathology results. Measurements (n = 75) were performed during the first 4 weeks posttransplantation by inserting the LDF flexible probe through the ileostomy for 25 to 30 cm. Forty-six of the 75 measurements were performed within 24 hours of endoscopy and biopsy. In uncomplicated cases, we recorded a gradual increase in mucosal perfusion during the first week posttransplantation that presumably reflected regeneration after reperfusion injury. Increased mucosal perfusion did not seem to correlate with rejection or other adverse clinical events. Sudden and sustained decreases in mucosal perfusion by 30% or more compared to the previous measurements were associated with septic episodes, rejection, or both. LDF revealed a good sensitivity in monitoring the intestinal microcirculation. It was able to indicate perfusion changes associated with acute rejection. The relatively low specificity of LDF may be compensated by the low invasivity, allowing frequent investigation. LDF may be an additional tool for routine monitoring of intestinal allografts.

Steroid-free immunosuppression in kidney transplant recipients and prograf monotherapy: an interim analysis of a prospective multicenter trial.

This report described an interim analysis of a investigator-driven multicenter trial in renal transplant recipients: the Prospective Quality of life Renal Transplantation Switch Study; Tacrolimus-based immunosuppression ("PQRST study"). Patients included in the trial initially treated with cyclosporine-based immunosuppression after renal transplantation who experienced side effects, such as hypertension, hyperlipidemia, hypertrichosis, or other adverse reactions, were converted to a tacrolimus-based immunosuppressive regimen (n = 31). Steroids were subsequently discontinued between 3 and 6 months after the conversion. As of today 19/31 (50%) patients have been successfully weaned off steroids with the remaining patients in this process. In this interim analysis, with a follow-up ranging from 1 to 18 months both patient and graft survivals were 100%. No patient experienced an acute rejection episode; none of the grafts were lost. Blood pressure decreased in 22/31 (71%) of the patients. No patient developed de novo diabetes or other serious side effect related to the conversion. Three patients were withdrawn from the trial because of side effects: bleeding, depression, and proteinuria. However, none of these adverse events were felt to be directly related to the change of the immunosuppressive regimen to tacrolimus monotherapy. In conclusion, conversion from cyclosporine to tacrolimus-based therapy was safe and well tolerated; it may improve the cardiovascular risk profile after kidney transplantation.

Regional cardiac tamponade: a hemodynamic study.

In 10 dogs, atrial tamponade, ventricular tamponade and then combined atrioventricular (AV) tamponade were produced at 10, 15 and 20 mm Hg intrapericardial pressure. Cardiac output decreased significantly at each level of cardiac tamponade; the changes in cardiac output and mean aortic pressure were comparable with atrial and ventricular tamponade. Combined atrial and ventricular tamponade produced significantly greater increases of right and left atrial pressure and significantly greater decreases of cardiac output than did either atrial or ventricular tamponade. During atrial tamponade only, a significant pressure gradient developed between the venae cavae and the right atrium. Compression of both ventricles by tamponade has a much greater hemodynamic effect than does compression of either ventricle alone. Compression of the entire heart has a greater hemodynamic effect than does compression of the atria alone or the ventricles alone. Compression of the great veins has a potential effect in tamponade, demonstrable when the ventricles could fill normally.

Influence of left ventricular dysfunction on the role of atrial contraction: an echocardiographic-hemodynamic study in dogs.

OBJECTIVES: The purpose of this study was to understand the significance of an effective atrial systole and the interactions between atrial and ventricular function. BACKGROUND: The significance of atrial function is controversial, particularly in the setting of left ventricular (LV) dysfunction. METHODS: Serial, rapid pacing in five dogs that had undergone radiofrequency ablation and implantation of right atrial and ventricular pacemakers produced reversible atrial and ventricular dysfunction (alone and in combination). Atrial function (echocardiograph-determined transmitral diastolic flow, left atrial appendage emptying, and pulmonary venous flow), cardiac output, and right heart pressures were measured at matched paced heart rates of 80 beats/min. RESULTS: Isolated rapid atrial pacing (LV ejection fraction approximately 60%) decreased atrial booster pump in the body and appendage of the left atrium, but increased the conduit function of the left atrium. Isolated LV dysfunction (LV ejection fraction approximately 34%) increased atrial booster pump function. The decreased atrial booster pump function in animals with combined atrial and ventricular dysfunction was incompletely compensated by the redistribution of the reservoir and conduit functions of the left atrium. As a result, cardiac output decreased and right heart pressures increased only after superimposed pacing. CONCLUSIONS: In the presence of a normal left ventricle (LV), atrial failure has little effect on cardiac output and right heart pressures because of compensatory conduit function, but when early LV dysfunction coexists, changes in reservoir and conduit functions are insufficient to compensate for an impairment of atrial contraction.

Cardiac tamponade: a comparison of right versus left heart compression.

It has been postulated that in cardiac tamponade, the hemodynamic effects of compression of the right heart chambers and great veins are more important than are the effects of left heart compression. In 10 anesthetized dogs with surgically compartmented pericardium, the hemodynamic effects of right atrial and right ventricular compression were compared with the hemodynamic effects of left atrial and left ventricular compression. The effects of right heart compression, left heart compression, and then effects of combined right and left heart compression, were compared at three levels of intrapericardial pressure: 10, 15 and 20 mm Hg. Aortic mean pressure decreased significantly at each level of intrapericardial pressure with right-sided tamponade but not with left-sided tamponade. Left atrial mean pressures decreased significantly with right-sided tamponade and increased with left-sided and combined tamponade. Right atrial mean pressures increased significantly with right-sided and combined tamponade, but not with left-sided tamponade. Heart rate increased significantly with each of the three varieties of tamponade. Cardiac output and stroke volume, which decreased with each variety of tamponade, were significantly lower during right-sided than during left-sided tamponade. Combined tamponade lowered stroke volume more than did right-sided tamponade, and lowered cardiac output more at 15 and 20 mm Hg intrapericardial pressure. It is concluded that, in this preparation, right-sided cardiac compression has more important hemodynamic effects than does left-sided compression. However, left-sided tamponade still makes a significant contribution to the total hemodynamic picture of cardiac tamponade.

Influence of acutely altered loading conditions on left atrial appendage flow velocities.

OBJECTIVES: The purpose of this study was to identify the effects of altered loading conditions on left atrial appendage flow velocities. BACKGROUND: Although studies have suggested that Doppler analysis of left atrial appendage blood flow may have clinical utility, the hemodynamic and cardiac mechanical determinants of left atrial appendage flow are poorly understood. METHODS: Transesophageal Doppler echocardiography was performed in eight atrially paced anesthetized dogs instrumented with sonomicrometers on the left atrial appendage and the left ventricular minor axis and with left atrial and left ventricular micromanometers. Left atrial appendage emptying and filling velocities corresponding to early and late ventricular diastole, respectively, were measured using volume expansion and phenylephrine infusion. RESULTS: Volume infusion caused a significant decrease in the early to late emptying and filling ratios (mean +/- SD 0.85 +/- 0.24 vs. 0.46 +/- 0.17 and 0.80 +/- 0.50 vs. 0.40 +/- 0.20, both p < 0.05). By contrast, phenylephrine infusion did not significantly alter either filling or emptying ratio. The independent determinants of each flow wave were identified with multiple regression analysis: early emptying velocity--time constant of left ventricular relaxation, left ventricular end-systolic dimension and aortic pressure (r = 0.75, p < 0.001); late emptying velocity--left ventricular peak positive time derivative of left ventricular pressure (dP/dt) and fractional shortening (r = 0.74, p < 0.001); early filling velocity--left atrial appendage shortening fraction (r = 0.45, p = 0.01) and late filling velocity--left atrial appendage lengthening rate and left ventricular fractional shortening (r = 0.56, p < 0.01). CONCLUSIONS: These results indicate that 1) both the magnitude and the pattern of left atrial appendage emptying and filling velocities are dependent on loading conditions, and 2) left atrial appendage velocities are influenced to a greater extent by changes in left ventricular than in left atrial appendage function. These findings may have implications for the pathogenesis of left atrial appendage thrombi.

Hemodynamic and regional blood flow distribution responses to dextran, hydralazine, isoproterenol and amrinone during experimental cardiac tamponade.

Four different interventions were examined in dogs with cardiac tamponade. Infusion of 216 to 288 ml saline solution into the pericardium reduced cardiac output from 3.5 +/- 0.3 to 1.7 +/- 0.2 liters/min as systemic vascular resistance increased from 4,110 +/- 281 to 6,370 +/- 424 dynes . s . cm-5. Left ventricular epicardial and endocardial blood flows were 178 +/- 13 and 220 +/- 12 ml/min per 100 g, respectively, and decreased to 72 +/- 14 and 78 +/- 11 ml/min per 100 g with tamponade. Reductions of 25 to 65% occurred in visceral and brain blood flows and in a composite brain sample. Cardiac output during tamponade was significantly increased by isoproterenol, 0.5 microgram/kg per min intravenously; hydralazine, 40 mg intravenously; dextran infusion or combined hydralazine and dextran, but not by amrinone. Total systemic vascular resistance was reduced by all interventions. Left ventricular epicardial flow was increased by isoproterenol, hydralazine and the hydralazine-dextran combination. Endocardial flow was increased by amrinone and the combination of hydralazine and dextran. Right ventricular myocardial blood flow increased with all interventions except dextran. Kidney cortical and composite brain blood flows were increased by both dextran alone and by the hydralazine-dextran combinations. Blood flow to small intestine was increased by all interventions as was that to large intestine by all except amrinone and hydralazine. Liver blood flow response was variable. The most pronounced hemodynamic and tissue perfusion improvements during cardiac tamponade were effected by combined vasodilation-blood volume expansion with a hydralazine-dextran combination. Isoproterenol had as dramatic an effect but it was short-lived. Amrinone was the least effective intervention.

Hemodynamic efficacy of rapid saline infusion and dobutamine versus saline infusion alone in a model of cardiac rupture.

Despite recent reports describing survival after cardiac rupture, the effectiveness of circulatory support while awaiting definitive surgical treatment is controversial. To assess the efficacy of volume expansion and pharmacologic support in cardiac tamponade due to cardiac rupture, a model of hemorrhagic cardiac tamponade was developed and treatment with rapid saline infusion and dobutamine was compared with rapid saline infusion alone in 15 closed chest dogs. A right ventricular wound of reproducible size was produced by deflating an aortic valvuloplasty balloon that had previously been passed by way of the internal jugular vein into the pericardial space and through a stab wound in the right ventricular free wall. Hemodynamic values were compared at baseline, during tamponade and after a rapid infusion (1 liter at 100 ml/min) of either saline solution alone or saline solution plus dobutamine (20 micrograms/kg per min). Atrial and pericardial pressures increased significantly in both groups. Mean arterial pressure, cardiac output and stroke volume increased with combined saline and dobutamine infusion to values similar to those at baseline (91 +/- 19%, 114 +/- 43% and 94 +/- 37% of baseline, respectively). In contrast, saline infusion alone caused a small increase in cardiac output but failed to significantly increase mean arterial pressure or stroke volume (76.8 +/- 14.2%, 55 +/- 18% and 51 +/- 17% of baseline, respectively). Combined rapid infusion of saline solution and dobutamine infusion has a more beneficial hemodynamic effect and may be more effective than rapid saline infusion alone in resuscitating patients with hemorrhagic cardiac tamponade due to cardiac rupture.

Mechanism of antiarrhythmic drug-induced changes in defibrillation threshold: role of potassium and sodium channel conductance.

OBJECTIVES: We sought to determine which ion current predominantly affects defibrillation outcomes by using specific pharmacologic probes (lidocaine [a sodium channel blocking agent] and cesium [an outward potassium channel blocking agent]) in 26 swine. BACKGROUND: The effect of a drug on sodium or potassium channel conductance, or both, may affect defibrillation threshold values. However, it is unknown which ion channel predominates. METHODS: Each pig was randomly assigned to one of four treatment groups with two treatment phases: group 1 = placebo (D5W) in treatment phase I followed by placebo plus cesium in treatment phase II (n = 6); group 2 = lidocaine followed by lidocaine plus placebo (n = 7); group 3 = lidocaine followed by lidocaine plus cesium (n = 7); group 4 = placebo followed by placebo plus placebo (n = 6). Defibrillation threshold values and electrocardiographic measurements were obtained at baseline and at treatment phases I and II. RESULTS: Lidocaine increased defibrillation threshold values from baseline by 71% in group 2 (p = 0.02) and by 92% in group 3 (p < 0.01). There were no changes in defibrillation threshold values from baseline to D5W in groups 1 and 4. When D5W was added to lidocaine in group 2 and D5W in group 4, there were no significant changes in defibrillation threshold values. However, when cesium was added to lidocaine in group 3, the elevated defibrillation threshold values (mean +/- SD) returned to baseline values (from 15.7 +/- 3.46 to 7.55 +/- 3.19 J, p < 0.01). Cesium added to D5W in group 1 also significantly reduced defibrillation threshold values from 7.10 +/- 1.27 to 4.14 +/- 1.75 J (p < 0.01). The effect of cesium on defibrillation threshold values was similar between groups 1 and 3, regardless of lidocaine, such that these values were reduced by 40 +/- 14% and 51 +/- 18%, respectively (p = 0.28). CONCLUSIONS: Cesium, through potassium blockade, reverses lidocaine-induced elevation in defibrillation threshold values. The magnitude of defibrillation threshold reduction when cesium was added to lidocaine was similar to the defibrillation threshold reduction when cesium was added to placebo. Thus, inhibiting outward potassium conductance and prolonging repolarization decreases defibrillation threshold values independent of sodium channel blockade.

Effect of congestive heart failure on in vivo canine aortic elastic properties.

OBJECTIVES: The aim of this study was to characterize fully in vivo aortic compliance over a wide range of passive distending pressures, and to study pharmacologically induced alterations in compliance using an intravascular ultrasound-based technique in the canine model of heart failure. BACKGROUND: Altered aortic compliance may influence considerably the function of the failing heart. Although some studies demonstrate that patients with heart failure have decreased aortic compliance, data from other studies are conflicting. METHODS: Aortic pressures and dimensions in seven dogs were determined both before and after pacing-induced congestive heart failure (CHF) using simultaneous micromanometer and intravascular ultrasound transducers. Decreases in aortic pressure were produced at baseline and after nitroprusside and dobutamine infusions. Inner and outer aortic circumferences were drawn at the lumen-intimal and media-adventitial borders. RESULTS: Aortic pressure-dimension (chamber) stiffness constants were greater after heart failure was produced (10.0+/-1.5 vs. 6.7+/-1.5, p < 0.05), but stress-strain stiffness (material) constants were similar (11.4+/-1.8 vs. 11.3+/-1.0, p=NS). Equivasodilating doses of nitroprusside and 10 microg/kg/min dobutamine decreased pressure-dimension stiffness constants after pacing-induced heart failure but not beforehand. The aortic wall thickness to diameter ratio was significantly greater in CHF than in the control condition (0.30+/-0.08 vs. 0.16+/-0.03, p < 0.01). CONCLUSIONS: Aortic compliance is decreased in this model of CHF, and this change is attributable primarily to vessel geometry rather than material properties. Equivasodilating doses of nitroprusside and equivalent doses of dobutamine increase aortic chamber compliance in dogs with CHF, but not in normal dogs. These data suggest that the beneficial effects of nitroprusside and dobutamine in CHF occur in part from improvement in aortic compliance.

Left atrial mechanical and biochemical adaptation to pacing induced heart failure.

OBJECTIVE: To determine the left atrial mechanical and biochemical adaptations to congestive heart failure, 10 dogs with rapid atrial and ventricular pacing and seven control dogs were studied. METHODS: Animals were instrumented with left atrial sonomicrometers and micromanometers and left atrial pressure-volume relationships were generated by phenylephrine boluses for maximum elastance (Emax) and end systolic elastance (Ees) calculations. Left atrial maximum volume, ejection fraction, and mean circumferential fibre shortening (Vcf) were compared at matched left atrial pressure. At necropsy, myosin heavy chain (MHC) isoforms from the left atrial body and appendage were separated with SDS-PAGE, stained with monoclonal antibodies to alpha and beta MHC, and quantified with laser densitometry. RESULTS: Left atrial ejection fraction and Vcf were significantly lower and maximum atrial volume and atrial systolic stroke volume were significantly greater in heart failure than in control. Emax was not significantly altered in heart failure, at 5.9(SD 2.9) v 4.5(1.6) mm Hg.ml-1 in controls. However, Vcf was lower (P < 0.05) and the A loop pressure-volume area (an index of eternal mechanical work performed by the left atrium) was greater (P < 0.05) in heart failure than in control dogs. The percent beta MHC in the left atrial body was greater in dogs with heart failure than in controls, at 42.6(9.8) v 17.3(9.0)%, P < 0.05. By contrast there was no significant beta MHC isoform switch in the left atrial appendage [14.4(7.6) v 17.9(9.7)%]. CONCLUSIONS: In this model of left atrial pressure and volume overload, there is significant upregulation of beta MHC in the left atrial body but not in the appendage and this isoform switch is associated with decreased velocity of left atrial contraction, increased atrial mechanical work, and unchanged force generation.

Effects of pericardiectomy on canine pulmonary blood volume during hypervolaemia.

STUDY OBJECTIVE: The aim was to determine the effect of the pericardium on the pulmonary blood volume response to intravascular volume loading. DESIGN: Changes in pulmonary lung volume were measured from radioactive counts over the lung during radionuclide ventriculography. Baseline measurements, and repeat measurements after infusion of 21 ml.kg-1 of the dog's own blood, were made both before and after a pericardiectomy. SUBJECTS: Ten closed chest, anaesthetised dogs were studied. MEASUREMENTS AND MAIN RESULTS: Prior to and following pericardiectomy, volume loading produced equivalent and significant increases in left atrial, mean pulmonary artery, and right atrial pressures (all p less than 0.05). Before pericardiectomy, radionuclide lung counts increased from 1606(SEM 348) to 1870(402) with volume loading, corresponding to a 16% rise in lung counts from baseline (p less than 0.05). Following pericardiectomy, a similar volume load did not result in a significant rise in lung counts [1588(245) to 1697(255), 9%, p = 0.16], but was accompanied by an increase in left ventricular diastolic volume, from 39.7(6.6) to 58.7(6.4) ml, p less than 0.05, and a decrease in systemic vascular resistance index, from 122,600(14,600) to 86,600(10,000) dynes.s.cm-5 x kg, p less than 0.05. CONCLUSIONS: These data support the concept that removal of the pericardium is accompanied by reduced pulmonary blood volume overload in response to intravascular volume loading. The mechanism appears to be related to improved left ventricular diastolic filling, perhaps the result of diminished ventricular interaction, and to redistribution of excess intravascular volume from the pulmonary to the systemic circuit.

Comparative assessment of regional left atrial perfusion by laser Doppler and radionuclide microsphere techniques.

OBJECTIVE: The aim was to study the relation between left atrial microcirculatory flux, using laser Doppler flowmetry (LDF), and blood flow, using radiolabelled microspheres (MS). METHODS: Studies were done in five anaesthetised dogs. LDF probes were sewn to the appendage and body of the left atrium. Radionuclide spheres (15 microns) were used to quantitate blood flow at baseline, and during atrial pacing at 3.5 Hz, atrial fibrillation, and intravenous adenosine infusion (1 mg.kg-1 x min-1). RESULTS: In the left atrial body, both MS and LDF perfusion increased significantly during pacing and adenosine infusion; only LDF registered significant increases during atrial fibrillation. In the left atrial appendage, MS flow failed to increase significantly with any intervention and LDF perfusion increased significantly only during atrial fibrillation. There was a significant but weak correlation (r = 0.36, p < 0.05) between LDF and MS when data from all sample sites (n = 40) were compared, but good correlation when only baseline and pacing data were compared (r = 0.72, p = 0.0004, n = 20). In four additional dogs with heart failure [mean left atrial pressure 25.3(SD 7.4) mm Hg] produced by three weeks of rapid right ventricular pacing, flux values at baseline were increased significantly compared to control dogs and the responses registered by LDF to pacing, atrial fibrillation, and adenosine infusion were attenuated markedly. CONCLUSIONS: (1) Microcirculatory flux detected by LDF can identify the direction, and to a lesser extent, the magnitude of changes in regional atrial perfusion; and (2) LDF may be useful in identifying abnormalities of vasodilator reserve that accompany chronic left atrial myocardial dysfunction.